Concerns about late-stage trials of Chinese vaccine

Bangladeshi universities and research organisations are working on late-stage human trials of a COVID-19 vaccine developed by Chinese company Sinovac Biotech Ltd, with Sinovac bearing the costs of the trials.

However, some immunologists have raised ethical issues about the trial which will test the vaccine candidate’s efficacy and safety.

Bangladesh’s Health Secretary, Md Abdul Mannan, said at a media briefing at his office on 21 September that the trial would start in a few days. He said Sinovac Biotech Ltd would send a letter to the health ministry with details in a day or two.

Earlier this month, Bangladesh’s Health Minister, Zahid Maleque, announced that the government had approved Sinovac’s phase III trial and noted that Bangladesh will get 100,000 free vaccine doses from Sinovac Biotech Ltd as part of the agreement.

In the initial stage, 4,200 healthcare workers at seven COVID-19 dedicated hospitals in Dhaka will take part in the trial process. Half the participants will take the vaccine.

The hospitals are Dhaka Medical College and Hospital (two units), Mugda General Hospital, Kurmitola General Hospital, Kuwait-Bangladesh Friendship Government Hospital, Dhaka Mahanagar General Hospital, and Holy Family Red Crescent Medical College Hospital.

The trials will be conducted by the internationally recognised Bangladeshi health research organisation International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDRB). Korea-based clinical research organisation LSK Global PS will monitor the trial.

Maleque also said that Bangladesh is in close contact with five other pharmaceutical companies working on COVID-19 vaccines.

Efficacy concerns

However, there have been concerns about the trials in Bangladesh. Concerns have arisen because of the race to find a vaccine, with unverified reports of China and Russia cutting corners before stage III trials are complete.

Sinovac’s CoronaVac vaccine has already been approved for emergency use in China as part of its programme to vaccinate high-risk groups such as medical staff and it has been administered in China within these limited groups since July. Officially, little information has been released about such use and how many people have been vaccinated.

As of 24 September, there have been almost 354,000 cases and 5,044 deaths from COVID-19 in Bangladesh. Sinovac first approached the Bangladesh authorities in July, as the number of cases in China had fallen to a level too low for trials. A smaller Sinovac trial is currently being conducted in Indonesia.

Three leading immunologists have also questioned the vaccine-candidate’s effectiveness. The project lead at WHO-Utrecht Centre of Excellence for Affordable Biotherapeutics Rezaul Karim; National Institutes of Health, US, immunologists Jubayer Rahman and Md Shamsul Alam have expressed concerns about the safety of the Sinovac vaccine trial in Bangladesh and raised questions about its effectiveness, in particular pointing to claims that the Sinovac vaccine has not induced neutralising antibodies against SARS-CoV-2 which causes COVID-19.

“It seems that those ICDDRB scientists are biased (non-scientifically) to this vaccine candidate, which induces poor antibody titers,” they wrote in an opinion piece in Bangladesh’s English language daily Dhaka Tribune.

Titers are laboratory tests that measure the presence and number of antibodies in blood. A titer may be used to prove immunity to disease.

They said neutralising antibody levels induced by Sinova’s candidate vaccine are much lower compared to convalescent sera (23.8 to 65.4 by vaccination compared to 163.7 in convalescent sera), even significantly decreased in the oldest group of individuals (59 years old).

They also added that “clearly, no T cell responses have been reported.”

Trials ‘are ethical’, government says

However, the Bangladesh authorities have insisted the trials are ethical. “We have given ethical permission for the trial after reviewing the research protocol,” Bangladesh’s state medical research council Bangladesh Medical Research Council (BMRC) director Mahmood Uz Jahan said in an interview with Reuters news agency.

He declined to comment when University World News reached out to him about the research protocol and ethical issues over several emails and phone calls on Tuesday. He said he is not the authority to comment on this.

Despite repeated telephone and email attempts by University World News, ICDDRB did not respond to requests for a comment.

Bangladeshi Health Officials said that Bangladesh also proposed a trial of the Sputnik V vaccine produced by Russia.

“We proposed a trial of the vaccine in Bangladesh before its marketing and they said that they would consider the proposal and expressed desire to continue communication,” Bangladesh’s English language daily New Age quoted National Health Advisory Committee Chairman Md Shahidullah as saying.

The Bangladesh government made the proposal as Russian Direct Investment Fund deputy vice-president Alexander Dzhabarov on Wednesday offered in an online meeting to sell the vaccine in Bangladesh in November.

Collaborations with universities

In another initiative, two Bangladeshi universities, BRAC University and Bangladesh University of Engineering and Technology, are collaborating with two United Kingdom universities in an effort to create a blueprint that will help ensure medical personnel can get a COVID-19 vaccine to everyone in need.

Supported by UK Research and Innovation (UKRI), an international team of researchers will assess the capacity and preparedness of Bangladesh’s cold-chain framework. They will create a roadmap and model for global COVID-19 vaccination.

Scientists at the University of Birmingham and Heriot-Watt University are leading the project with the two Bangladeshi universities.

“We will assess the capacity and preparedness of COVID-19 vaccines in Bangladesh. The one-and-a-half year long research project has just started and we are currently working on the questionnaire, ethical review, literature review and so on,” Farzana Munshi, PhD, a professor with Bangladesh’s BRAC University told University World News.

“Vaccination of COVID-19 will require a new fast-track approach to assess, re-engineer and build out the cold-chain logistics assets. This project will assist policy-makers in designing policies on the most sustainable interventions on medical supply chain at regional and national scale for COVID-19 [and] also other potential future natural disasters and epidemics,” she added.

Christopher Green, senior clinical lecturer in infectious diseases at the University of Birmingham, who is leading on many of the UK’s National Institute for Health Research’s urgent public research studies into COVID-19, including the vaccine trials under way in the West Midlands, said in a statement that delivery infrastructure is crucial in ensuring safe and effective COVID-19 vaccination.

“The development of a safe and effective COVID-19 vaccine is of the highest global health priority, but a COVID-19 vaccine will only reach its full potential when matched with a delivery infrastructure that can reach as far as those who need it, and for it to be sustainable for the future needs of the community,” he said.